Transplant Trial Watch

A novel MSC-based immune induction strategy for ABO-incompatible liver transplantation: a phase I/II randomized, open-label, controlled trial.

Zhang, Y., et al

Stem Cell Research & Therapy 2021; 12(1): 244.


Aims
The aim of this study was to assess the feasibility and safety of using mesenchymal stem cells (MSCs) as a replacement for rituximab in ABO-incompatible liver transplantation (ABO-i LT).

Interventions
Participants were randomised to either the rituximab group or the MSC group.

Participants
22 patients receiving ABO-incompatible liver transplantation.

Outcomes
Primary outcomes included the assessment of MSC-related adverse events, incidence of antibody-mediated rejection (AMR) and acute cellular rejection (ACR). The secondary outcomes included graft survival and recipient survival, and the incidence of posttransplant complications (including biliary complications and specific infections).

Follow-up
2 years

CET Conclusions
This is a very interesting RCT in ABO incompatible liver transplantation. This high risk subgroup of liver transplantation may be required for patients in desperate need of a liver and comes with high risks of rejection, infection and hepatic artery thrombosis. In this study, the control drug for immune induction was rituximab and this was compared to mesenchymal stem cells (MSC) as the study intervention. The trial is randomised, but the method of randomisation is not fully described so we cannot be sure it was free from bias. Also, the study was open-label and this is another potential avenue for bias. The primary endpoint was the tolerability and safety of multidose MSC administration in this population and the therapy appears to be well tolerated from the results of this study. The trial is too small to be powered to assess the secondary outcomes fully; despite an apparently large reduction in acute rejection, it is not statistically significant. There was, however, a significant reduction in sepsis episodes with MSC compared to Rituximab, and also a significant reduction in biliary complications. These results need to be viewed in the context of an unblinded trial. This study does however provide an informative stepping stone towards a larger RCT to properly assess the comparative effects of MSC in ABO incompatible liver transplantation, and the authors have such a trial registered (ChiCTR2000037732).

Jadad score
2

Data analysis
Strict intention-to-treat analysis

Allocation concealment
No

Trial registration
ChiCTR2000037732

Funding source
Non-industry funded